title: TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements.
abstract: Dyskeratosis congenita (DC) is a rare inherited form of bone marrow failure (BMF) caused by mutations in telomere maintaining genes including TERC and TERT. Here we studied the prevalence of TERC and TERT gene mutations and of telomere shortening in an unselected population of patients with BMF at our medical center and in a selected group of patients referred from outside institutions. Less than 5% of patients with BMF had pathogenic mutations in TERC or TERT. In patients with BMF, pathogenic TERC or TERT gene mutations were invariably associated with marked telomere shortening (<< 1st percentile) in peripheral blood mononuclear cells (PBMCs). In asymptomatic family members, however, telomere length was not a reliable predictor for the presence or absence of a TERC or TERT gene mutation. Telomere shortening was not pathognomonic of DC, as approximately 30% of patients with BMF due to other causes had PBMC telomere lengths at the 1st percentile or lower. We conclude that in the setting of BMF, measurement of telomere length is a sensitive but nonspecific screening method for DC. In the absence of BMF, telomere length measurements should be interpreted with caution.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Du
authors.forename: Elena
authors.initials: E
authors.lastname: Pumbo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ivanovich
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Ulrike M
authors.initials: UM
authors.lastname: Reiss
authors.forename: Deborah
authors.initials: D
authors.lastname: Chirnomas
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimamura
authors.forename: Adrianna
authors.initials: A
authors.lastname: Vlachos
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Lipton
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Goyal
authors.forename: Frederick
authors.initials: F
authors.lastname: Goldman
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mason
authors.forename: Monica
authors.initials: M
authors.lastname: Bessler
mesh_terms: D000328:Adult; D001855:Bone Marrow Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019871:Dyskeratosis Congenita / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase